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Development and production of positron emission tomography radiopharmaceuticals for diagnostic purposes in oncology


Radiopharmaceuticals are agents (medicines, biological products) labeled with radionuclides and widely used in the field of nuclear medicine as tracers in the diagnosis and treatment of many diseases, including cancer. Over the past 50 years, nuclear medicine research centers around the world have invested much effort in developing new radiopharmaceuticals for application in cancer imaging and therapy. In Brazil, the production of radiopharmaceuticals for medical purposes was a Monopoly up to 2006, and during this period the investment in research and development was not enough to sustain growth. Currently, 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is the only PET tracer produced in Brazil and it is the most widely used tracer for studies of tumor metabolism in oncology. However, FDG accumulation is not specific to tumors and can be present in various conditions including inflammation and benign processes. These limitations have prompted research into more specific biomarkers of cancer. The main purpose of this project is to start a new line of independent research with focus on the design and development of new radiotracers for PET (18F) imaging in oncology. Therefore, we propose the synthesis of novel tracers able to: (1) detect the expression of angiotensin II receptors in tumors; (2) detect the presence and extent of hypoxia within the tumor microenvironment and; (3) determine the glycosylation pattern associated with tumor progression in vivo. We also propose to study the biodistribution of bio-molecules associated with tumor progression and evaluate new anti-cancer therapy approaches taking advantage of the use of radiopharmaceuticals described in the literature. It should be noted that these new tracers were proposed so that we could work together with research teams of recognized scientific competence in Sao Paulo State as well as optimize resource utilization. In addition, the synthesis of known tracers will favor integration between research groups and institutions located in the Clinics Hospital complex and open new perspectives in cancer research. A major challenge to overcome is the establishment of the necessary conditions for the synthesis and development of 18F-labeled bio-molecules in the center for preclinical research at the SMN-InRad-HC-FMUSP (Department of Nuclear Medicine of the Institute of Radiology, Clinics Hospital and Faculty of Medicine of the University of São Paulo). After overcoming the initial challenge of setting up the laboratory infrastructure, the project will lead to an increase in the human resources capabilities and prepare professionals in several research areas, such as: Chemistry, Pharmacy, Physics, Biology, and Medicine. Finally, it will contribute to the further development of molecular imaging research at the InRad HC-FMUSP. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DOS SANTOS, SOFIA NASCIMENTO; SHELDON, HELEN; PEREIRA, JONATHAS XAVIER; PALUCH, CHRISTOPHER; BRIDGES, ESTHER M.; EL-CHEIKH, MARCIA CURRY; HARRIS, ADRIAN L.; BERNARDES, EMERSON SOARES. Galectin-3 acts as an angiogenic switch to induce tumor angiogenesis via Jagged-1/Notch activation. ONCOTARGET, v. 8, n. 30, p. 49484-49501, . (12/06875-6)
SANTOS, SOFIA N.; JUNQUEIRA, MARA S.; FRANCISCO, GUILHERME; VILANOVA, MANUEL; MAGALHAES, ANA; BARUFFI, MARCELO DIAS; CHAMMAS, ROGER; HARRIS, ADRIAN L.; REIS, CELSO A.; BERNARDES, EMERSON S.. O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer. ONCOTARGET, v. 7, n. 50, p. 83570-83587, . (12/06875-6)
ORTEGA PIJEIRA, MARTHA SAHYLI; GONCALVES NUNES, PAULO SERGIO; DOS SANTOS, SOFIA NASCIMENTO; ZHANG, ZHENGXING; NARIO, ARIAN PEREZ; PERINI, EFRAIN ARAUJO; TURATO, WALTER MIGUEL; RIERA, ZALUA RODRIGUEZ; CHAMMAS, ROGER; ELSINGA, PHILIP H.; et al. Synthesis and Evaluation of [F-18]FEtLos and [F-18]AMBF(3)Los as Novel F-18-Labelled Losartan Derivatives for Molecular Imaging of Angiotensin II Type 1 Receptors. Molecules, v. 25, n. 8, . (12/06875-6)
FERMIN, MARISE L.; DYLON, L. SEBASTIAN D.; CECILIO, NERRY T.; SANTOS, SOFIA N.; TOSCANO, MARTA A.; DIAS-BARUFFI, MARCELO; ROQUE-BARREIRA, MARIA C.; RABINOVICH, GABRIEL A.; BERNARDES, EMERSON S.. Lack of galectin-3 increases Jagged1/Notch activation in bone marrow-derived dendritic cells and promotes dysregulation of T helper cell polarization. Molecular Immunology, v. 76, p. 22-34, . (12/06875-6)

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